The Perinatal Project is one of two longitudinal studies of schizophrenia development (the other is the Danish High-Risk Study begun in 1962). From 1959 to 1993, Dr. Mednick and colleagues examined and followed genetically-at-risk subjects and controls. In order to better study perinatal factors, Dr. Mednick initiated this longitudinal study of children of parents with schizophrenia, for whom excellent prospective perinatal data existed. Subjects were a part of a major perinatal cohort study begun in 1959 of 9,182 consecutive deliveries in Copenhagen. For controls, the study used children from this cohort with parents with a non-psychotic disorder and children whose parents did not have a diagnosed psychiatric disorder. In 1972 a group of 265 participants, 11-13 years of age, with severely psychiatrically ill parents, as well as controls, were examined. The assessment included a formal neurological examination, measures of laterality, assessment of neuromotor functioning, and neuropsychological examinations. In December, 1993 (21 years after the initial assessment) colleagues completed a follow-up diagnostic study of these participants (then 32-34 years of age). Based on interview and/or hospital records, we obtained adult diagnostic outcomes for 242 of the 265 subjects. Sixteen patients with schizophrenia have been identified, and 10 others have been diagnosed with a schizophrenia- spectrum disorder. Seventy subjects were diagnosed with a non-psychotic disorder, and 146 subjects were judged to have no mental illness. The current study proposes to determine whether prenatal influence, neurological information at one year of age, and preadolescent behaviors can be combined to predict schizophrenia in adulthood. Several publications from this study have begun to describe the premorbid course of schizophrenia (see preliminary studies).These indicators have not, however, been studied collectively with regard to an outcome of schizophrenia-spectrum disorder. The specific aims of this project are to: 1) Make use of this existing database to determine the ability of individual and combined prospective neurological childhood measures to predict adult schizophrenia-spectrum outcome. 2) Examine prenatal and perinatal factors in the database in relation to neurological dysfunction to help understand the origins of neurological dysfunction. It is hoped that this study will increase the ability to identify youth at risk for the future development of schizophrenia spectrum disorders. This study will attempt to accomplish this goal through the comprehensive investigation of very early risk factors (pregnancy and birth complications) and neurological signs in pre- adolescence among youth at genetic risk for schizophrenia. In addition to prediction, information from this project will be useful in understanding the origins of schizophrenia spectrum disorders. This project proposes to use premorbid, prospective, structured assessments of multiple factors already shown to relate to schizophrenia individually, to provide increased accuracy in prediction of youth who later develop schizophrenia-spectrum disorders. With the many potential advantages of early identification and perhaps early intervention, this project could potentially bridge a gap between traditional premorbid research and more recent prodromal research, providing clinically relevant predictive variables for consideration in the identification of youth at risk for psychosis. [unreadable] [unreadable] [unreadable]